Nate Traaseth, Ph.D.

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SUMMARY

The research team led by Nate Traaseth, Ph.D., studies molecular mechanisms of antibiotic resistance, cancer and childhood developmental disorders. Deciphering these mechanisms at the atomic scale involves a combination of structural, computational and biological approaches to develop structure-activity relationships. The knowledge gained guides the discovery of potent and selective compounds targeting proteins central to these diseases. Projects in the laboratory focus on membrane protein transporters involved in the movement of antibiotics and substrates across the membrane. They also focus on receptor tyrosine kinases involved in mediating cellular signaling cascades that result in cell growth, development and metabolism. Due to the challenges in studying membrane proteins, the Traaseth laboratory also develops methods to make studying structure and dynamics on these systems more feasible.

Focus areas

• Antibiotic resistance. Bacteria gain antibiotic resistance through several mechanisms, including drug efflux, target protein mutations, reduced drug permeability and drug breakdown. One of the broadest defense mechanisms studied in the Traaseth laboratory involves efflux pumps that bind and transport antibiotics out of the cell. The goal of this project is to understand the transport mechanism and use this knowledge to design inhibitors that selectively block efflux.
• Cellular signaling mediated by receptor tyrosine kinases. Receptor tyrosine kinase genes regulate essential biological processes in humans, including embryogenesis, adult tissue homeostasis and metabolism. These genes display differential spatiotemporal expression during development and throughout adulthood. Improper regulation of these proteins leads to human diseases such as cancer and childhood developmental disorders. The goal of this project is to elucidate molecular mechanisms that govern RTK regulation in human health and disease.
• Protein mechanisms. The Traaseth laboratory is fascinated by how proteins accomplish functions. To determine how these molecular machines work, the laboratory uses a combination of cryoelectron microscopy to reveal structures and conformations present in the ensemble, nuclear magnetic resonance (NMR) spectroscopy to probe dynamics, and computational approaches to provide atomic resolution insight. Findings from these approaches are used in conjunction with functional measurements to construct structure-activity correlations.
• Method development. The Traaseth laboratory develops approaches for enhancing the sensitivity and ability to apply cryoelectron microscopy and NMR spectroscopy to study challenging biomolecular systems. These innovations enable faster and more accurate analyses of membrane proteins, which are among the most common drug targets.

Significance to patient care

Dr. Traaseth and his team are working to stop antibiotic resistance, which happens when bacteria no longer respond to medicines that used to kill them. Their research helps us understand how bacteria avoid antibiotics and looks for new ways to stop this from happening. This could make current antibiotics more effective and help people recover faster. The team also studies how changes in our genes can affect tiny parts of our cells called proteins. These changes sometimes lead to serious health problems like cancer or childhood developmental disorders. By learning more about these changes, the Traaseth Laboratory hopes to discover better treatments and improve care for patients.

Professional highlights

• National Research Scholar Development K22 Award, National Institute of Allergy and Infectious Diseases, 2011-2013.
• University of Minnesota:
  • Boyer Award for Postdoctoral Excellence, Department of Biochemistry, Molecular Biology, and Biophysics, 2008.
  • John Overend Award for Graduate Research in Physical Chemistry, Department of Chemistry, 2007.